The University of Michigan proposes to renew funding for its Rheumatic Diseases Research Core Center (UM-RDCC). The UM-RDCC is a broadly based effort involving approximately eighty faculty, who seek to apply a broad range of research skills, backgrounds, and approaches to investigation of fundamental issues in the etiology and pathogenesis of rheumatic diseases and in development of a scientific basis for novel therapeutics. The UM-RDCC will foster collaborations between investigators in thematic areas of research strength and interest, such as development and testing of innovative therapeutics, analysis of immune mechanisms in rheumatic diseases and investigation of organ-targeted inflammatory and tissue remodeling pathways. The UM-RDCC will also foster disease focused laboratory and translational research linked to clinical research programs. Activities in the Center will be supported by six Biomedical Core Facilities, including Flow Cytometry, Hybridoma, Vector, Transgenic Animal, Protein Structure, and Microarray. Three Pilot and Feasibility Projects are proposed, two of which are led by new faculty recently recruited to the UMRDCC, whose focus is the pathogenesis of inflammatory arthritis. The third Pilot and Feasibility Project is led by an experienced dermatology investigator who will mechanistically investigate a highly innovative approach to treating scleroderma. The UM-RDCC and its administrative unit will be directed by David A. Fox, M.D., who has fifteen years of experience in administration of broadly based, NIAMS-funded center programs. Rory Marks, M.D., Associate Professor of Rheumatology is proposed to continue as the UMRDCC Associate Director, with special responsibilities for supervision of the biomedical cores. The Center's administrative team will be assisted by an Executive Committee, an Internal Advisory Committee, and two External Scientific Advisors, Drs. Michael Brenner and Michael Holers. The UM-RDCC is constructed to maximally engage the talents and resources of the University of Michigan to focus on research in the rheumatic diseases. The Center leadership will maintain close links between the basic and pre-clinical research activities of the UM-RDCC and expanding clinical investigation in the rheumatic diseases at the University of Michigan, so as to maximize the impact of UM-RDCC discoveries on the health of patients with rheumatic diseases.